A new antiresorptive approach to the treatment of fragility fractures: long-term efficacy and safety of denosumab.

Abstract

An imbalance of the remodeling process for bone resorption leads to a loss of tissue with consequent microarchitectural damage, evident in conditions such as osteoporosis and related fragility fractures. Currently, pharmacological therapies are able to prevent or slow down bone resorption by inhibiting osteoclast activity. An innovative and targeted anti-resorptive approach is represented by the inhibition of RANK ligand (RANK-L), essential for the proliferation and activity of osteoclastic cells. The human monoclonal antibody against RANK-L (denosumab) has been approved for the treatment of osteoporosis. In clinical trials of patients with osteoporosis, inhibition of RANK-L has reduced bone loss and damage to the microarchitecture and was associated with an increase in mass and resistance at different skeletal sites, with most significant effects than those demonstrated by any other antiresorptive drugs. In addition, after 3 years of treatment, it showed a reduction in vertebral and non-vertebral fracture risk. Denosumab treatment also has not revealed any alteration in the physiological processes of fracture repair, showing no increase in the onset of complications 3 years after the fracture. The data show that denosumab offers an effective alternative therapeutic approach for the treatment of severe osteoporosis, with positive effects on BMD and reduction of fragility fractures risk. So, promising results in terms of therapeutic efficacy and reliability make desirable the wide clinical use of denosumab for the treatment of osteoporotic fractures in the near future.

• Authors: Umberto Tarantino, Monica Celi, Maurizio Feola, Federico Maria Liuni, Giuseppina Resmini, Giovanni Iolascon
• Journal: Aging clinical and experimental research (Aging Clin Exp Res) Vol. 25 Suppl 1 Pg. S65-9 (Oct 2013) ISSN: 1720-8319 [Electronic] Germany
• PMID: 24046047 (Publication Type: Journal Article, Review)

Chemical References

• Antibodies, Monoclonal, Humanized
• Bone Density Conservation Agents
• Osteoprotegerin
• RANK Ligand
• Denosumab

Topics

• Animals
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Bone Density
• Bone Density Conservation Agents (therapeutic use)
• Bone Resorption
• Bone and Bones
• Cell Proliferation
• Denosumab
• Female
• Fracture Healing (drug effects)
• Fractures, Bone (therapy)
• Humans
• Male
• Mice
• Osteoclasts (metabolism)
• Osteoporosis (drug therapy)
• Osteoporosis, Postmenopausal (drug therapy)
• Osteoprotegerin (metabolism)
• Postmenopause
• RANK Ligand (metabolism)
• Randomized Controlled Trials as Topic
• Treatment Outcome